Biomarker analysis from the phase 2b randomized placebo-controlled trial of riociguat in early diffuse cutaneous...

Area of Science:

• Biomarkers
• Pharmacology
• Rheumatology

Background:

• Systemic sclerosis (SSc) is a complex autoimmune disease characterized by fibrosis.
• Identifying effective treatments and predictive biomarkers for SSc is crucial.

Purpose of the Study:

• To evaluate disease and target engagement biomarkers for riociguat in early diffuse cutaneous systemic sclerosis (SSc).
• To assess the potential of these biomarkers in predicting treatment response.

Main Methods:

• The RISE-SSc trial randomized 121 patients to riociguat or placebo for 52 weeks.
• Biomarkers including plasma cyclic guanosine monophosphate (cGMP), serum sPECAM-1, CXCL-4, and skin α-smooth muscle actin (αSMA) were measured.

Main Results:

• Riociguat significantly increased plasma cGMP and decreased serum sPECAM-1 and CXCL-4 compared to placebo by week 14.
• No differences in skin collagen markers were observed between groups.
• Higher baseline sPECAM-1 or αSMA-positive cells predicted a greater reduction in skin score with riociguat.

Conclusions:

• Riociguat engages the nitric oxide-soluble guanylate cyclase-cGMP pathway.
• Riociguat reduced sPECAM-1, an angiogenic biomarker, in SSc patients.
• Elevated sPECAM-1 and αSMA may identify patients who benefit from riociguat for skin fibrosis.